Angiotensin II AT(1) receptors preserve vasodilator reactivity in skeletalmuscle resistance arteries

Resistance arteries (100-150 mm) were isolated from the gracilis muscle of normotensive Sprague-Dawley rats placed on a high-salt (HS) diet (4.0% NaCl ) for 3-7 days. Exposure to the HS diet eliminated vascular relaxation in r esponse to hypoxia (PO2 reduction to 35-40 Torr) and iloprost, a stable ana log of prostacyclin. Vasodilator responses were restored in arteries isolat ed from chronically instrumented HS rats receiving a continuous intravenous infusion of either angiotensin II (ANG II; 5-6 ng . kg(-1) . min(-1)) or A NG II plus the AT(2) receptor blocker PD-123319 (5 mug . kg(-1) . min(-1)) for 3 days before the isolated vessel studies. In contrast, coinfusion of t he AT(1) receptor blocker losartan (20 mug . kg(-1) . min(-1)) or coinfusio n of both receptor blockers with ANG II eliminated the protective effect of ANG II to restore dilator responses to hypoxia and iloprost. Neither a HS diet nor ANG II infusion affected the dilation of gracilis arteries in resp onse to direct activation of adenylyl cyclase by forskolin, suggesting that the effect of both the HS diet and the ANG II on the vasculature is mediat ed upstream from second messenger systems. These findings indicate that the protective effect of ANG II to maintain vasodilator reactivity in resistan ce arteries of rats on a HS diet is mediated via the AT(1) receptor subtype .